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Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia.
Braz J Med Biol Res. 2003 Oct; 36(10):1311-8.BJ

Abstract

Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH.

Authors+Show Affiliations

Departamento de Patologia Clínica, Faculdade de Ciências M dicas, Universidade Estadual de Campinas, Campinas, SP, Brasil.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14502362

Citation

Torres, N, et al. "Phenotype and Genotype Correlation of the Microconversion From the CYP21A1P to the CYP21A2 Gene in Congenital Adrenal Hyperplasia." Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas, vol. 36, no. 10, 2003, pp. 1311-8.
Torres N, Mello MP, Germano CM, et al. Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia. Braz J Med Biol Res. 2003;36(10):1311-8.
Torres, N., Mello, M. P., Germano, C. M., Elias, L. L., Moreira, A. C., & Castro, M. (2003). Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia. Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Medicas E Biologicas, 36(10), 1311-8.
Torres N, et al. Phenotype and Genotype Correlation of the Microconversion From the CYP21A1P to the CYP21A2 Gene in Congenital Adrenal Hyperplasia. Braz J Med Biol Res. 2003;36(10):1311-8. PubMed PMID: 14502362.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Phenotype and genotype correlation of the microconversion from the CYP21A1P to the CYP21A2 gene in congenital adrenal hyperplasia. AU - Torres,N, AU - Mello,M P, AU - Germano,C M R, AU - Elias,L L K, AU - Moreira,A C, AU - Castro,M, Y1 - 2003/09/16/ PY - 2003/9/23/pubmed PY - 2004/1/24/medline PY - 2003/9/23/entrez SP - 1311 EP - 8 JF - Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas JO - Braz J Med Biol Res VL - 36 IS - 10 N2 - Deficiency of 21-hydroxylase is the most common form of congenital adrenal hyperplasia (CAH-21OH). We determined by allele-specific PCR the frequency of microconversion in the CYP21A2 gene in 50 Brazilian patients with the classical (salt wasting: SW and simple virilizing: SV) forms and nonclassical (NC) form of CAH-21OH and correlated genotype with phenotype. Genotypes were classified into three mutation groups (A, B, and C) based on the amount of enzymatic activity in in vitro studies using adrenal cells. In 94 unrelated alleles, we diagnosed 76% of the affected alleles after screening for 7 microconversions. The most frequent point mutations observed in this series were I172N (19%), V281L (18%), and IVS2,A/C>G,-12 (15%). In the SW form, the most frequent mutation was IVS2,A/C>G,-12 (38%), in the SV form it was I172N (53%), and in the NC form it was V281L (57.7%). We observed a good correlation between genotype and phenotype. Discordance between genotype and phenotype was found in one SV patient with a mild mutation in one of the alleles (R356W/V281L). However, we cannot rule out the presence of an additional mutation in these alleles. We also observed a good correlation of genotype with 17alpha-hydroxyprogesterone, testosterone, and androstenedione levels. The severity of external genitalia virilization correlated with the severity of mutation. In conclusion, the frequencies described in the present study did not differ from worldwide studies, including the Brazilian population. The few differences observed may reflect individual sample variations. This new Brazilian cohort study suggests the presence of new mutations in Brazilian patients with different forms of CAH-21OH. SN - 0100-879X UR - https://www.unboundmedicine.com/medline/citation/14502362/Phenotype_and_genotype_correlation_of_the_microconversion_from_the_CYP21A1P_to_the_CYP21A2_gene_in_congenital_adrenal_hyperplasia_ L2 - https://www.scielo.br/scielo.php?script=sci_arttext&pid=S0100-879X2003001000006&lng=en&nrm=iso&tlng=en DB - PRIME DP - Unbound Medicine ER -